Pressurized metering dispenser

ABSTRACT

A pressurized metering dispenser comprises a main reservoir, a liquid metering chamber and a gas chamber. A valve arrangement enters the reservoir and the gas chamber from an outlet nozzle at the end of a central passage, the inboard end of which is above the level of liquid in the reservoir when the dispenser is held nozzle-down. A gas holding chamber communicates with the gas chamber and the liquid metering chamber with the reservoir in a normal state, and actuation is achieved by upward displacement of the nozzle to start off the liquid and gas holding chambers and from their supplies and finally cause the chamber to communicate with the chamber to cause the liquid to be expelled through the nozzle under the gas pressure in the chamber. A holder for such a dispenser includes an actuating lever and counter to indicate the number of actuations. A modified dispenser includes a sleeve which is resiliently displaceable relative to the lower end of a nozzle and indicates an extension of known internal volume into which liquid can be drawn by upward displacement, for mixing with reagent subsequently ejected through the nozzle on actuation of the dispenser.

Field of the Invention

The present invention relates to a pressurised metering dispenser and toa holder and actuator for pressurised metering dispensers.

Background of the Invention

Metering liquid dispensers using gas pressure for discharging the liquidwere invented in the 1950's. As with most common pressurised liquiddispensers, the liquid in such known metering dispensers is subdividedinto minute droplets on leaving the dispenser, forming an aerosol.

The main use for such dispensers hitherto has been for administeringmetered doses of drugs for inhalation. Early forms of dispensers gavesomewhat erratic metering, but improvements in valve designs and informulations for the dispenser contents have led to pressurised meteringliquid dispensers currently available which are capable of ± 1% on thenominal metered volume dispensed.

However, further variations occur during the period of use of adispenser, reducing the overall dispensing accuracy to no better than ±5%. One cause for this problem is that as the dispenser is used highvapour pressure components in the dispenser contents are preferentiallydischarged, and therefore depleted. Thus, when the dispenser is nearlyempty the doses dispensed will have an increased concentration of lowvapour pressure components, and the concentration of the activepharmaceutical ingredient may vary during the course of use of thedispenser.

A typical formulation in a known pressurised metering liquid dispensersused to administer pharmaceuticals for inhalation contains thepharmaceutical active ingredient, a mixture of propellents (typicallyfluorocarbons, 11, 12 and 114), a low volatility excipient and valvelubricant such as sorbitan trioleate and anti-oxidants, in solution inethanol.

The dispensers perform their metering function by means of a meteringchamber located within the dispenser and normally open to the maindispenser reservoir containing the formulation. When the dispenser isheld in the correct position for use, the metering chamber is lowermostand filled with formulation. During actuation of the dispenser, themetering chamber is first closed from the main reservoir and thenconnected to a discharge passage. The pressure of the propellentscontained in the formulation will then drive the contents of themetering chamber out through the discharge passage. As the formulationis released into the atmosphere, any propellents still in liquid formwill tend to vaporise, assisting in the formation of the aerosol, andthe ethanol solvent will also tend to evaporate. This evaporation tendsto chill the discharge nozzle of the dispenser, and rapidly repeateddischarges from the dispenser may result in the nozzle freezing.

In my co-pending application Ser. Nos. 8608571 and 8624064, it issuggested that a pressurised 1-shot metering dispenser may be used todeliver reagents during chemical analysis. It has also now been realisedthat there are many other situations in which it would be convenient tobe able to deliver precisely metered volumes of liquid from apressurised dispenser. For example, in many circumstances in medicineand chemistry it is necessary to prepare a sample before it can beanalysed or studied. In such sample preparation, the sample may bediluted with distilled water or some other chemically pure diluant andstabilisers such as anti-oxidants, pH buffers etc may also be added. Allof these must be added in precisely known quantities if accurate resultsare to be obtained from subsequent study or analysis.

Typically, the dispensing of accurate volumes in such circumstances isat present carried out using various types of pipettes and syringes.There are three main types of devices in use. The first are "airpipettes", in which a squeeze-bulb or syringe sucks up liquid byreducing the air pressure in the pipette, and then small amounts ofliquid are dispensed by mechanically indexing a plunger. The second arepositive displacement syringes, in which a plunger is brought up to thetip of the discharge nozzle and the syringe is filled and emptied bymovement of the plunger. The third are single shot dispensers, whichemploy a pair of non-return valves and a syringe which is alternatelyfilled and emptied to discharge a fixed volume.

The first type is the least accurate because there is a volume of airbetween the reagent and the piston or plunger. The second type is themost accurate because it relies on the movement of a piston in a veryaccurate bore and there is no air cushion between the liquid and thepiston. The third type is less precise but is suitable for dispensingliquids from a bulk container. The best figure for repeatability of thevolume dispensed from one discharge to another of the same device isaround ± 1% for these types of device.

In addition to their lack of convenience, these devices suffer thefollowing problems. First, the reagent or other liquid has to be drawnfrom a bulk supply, or made up immediately prior to use if it has alimited shelf life, and in all pipetting methods the liquid is incontact with the air during the dispensing operation. This providesopportunities for the liquid being dispensed to become contaminated bydust, dirt and bacteria, and the liquid itself may undergo a changethrough evaporation, oxidation or the like. Second, occasionally adroplet of liquid remains on the tip of the discharge nozzle of thedevice, so that one measure is under-volume and the next measure isover-volume. The range of metered volumes dispensed from such apparatusis typically from about 5 microlitres to 10 milliliters, and a dropletcan represent a large percentage error at the lower end of this range.

In my earlier U.K. patent application Nos. 8608571 and 8624064, it isproposed that reagents for chemical analysis could be pre-packaged in apressurised metering dispenser, in which case contamination and errorsdue to droplets remaining on the discharge nozzle are much less likelyto occur. Additionally, the reagents can be made up by the manufacturerunder controlled conditions to ensure consistent high quality and can beused in an environment in which the preparation of a reagent or itsextraction from a bulk supply are impractical. The same principle can beused, and the same advantages obtained, in other circumstances in whicha precisely metered volume of liquid is required to be dispensed.

However, the variation in the composition of the contents of thedispenser during use, as referred to above, means that the conventionalarrangements for pressurised metering liquid dispensers cannot normallybe applied to chemical analysis sample preparation etc. Additionally, itis frequently a disadvantage when dispensing a metered volume of liquidfor the liquid to be dispensed in the form of an aerosol, whereas withthe conventional pressurised dispenser arrangement the formation of anaerosol as the liquid is discharged is usually unavoidable. Furthermore,it is sometimes desired to dispense a metered volume of the same liquidinto each of a series of containers in quick succession, in which casethe tendency of the nozzle of a conventional dispenser to freeze onrapid repetition of discharges is inconvenient.

These difficulties with known pressurised metering dispensers could belargely reduced if not overcome completely by replacing the conventionalfluorocarbon propollent with a pressurised chemically inert gaspropollent such as nitrogen or argon, as is proposed in my earlierapplications. In the prior art dispensers, the variation of thecomposition of the dispenser contents with use is largely due to highvapour pressure components in the propellent mix evaporatingpreferentially. If a compressed gas propellent is used in place of acondensed high vapour pressure substance the propellent does not dilutethe liquid composition in the dispenser and thus the pattern of loss ofpropellent will have no effect on the concentration or composition ofthe liquid being dispensed. Since the propellent is already gaseous andtends not to be mixed with the liquid during discharge, the formation ofan aerosol can normally be avoided if this is desired (although ifrequired an aerosol can be formed by appropriate shaping of thedischarge nozzle). Additionally, since the propellent is already gaseousit does not vapourise at the discharge nozzle so that the cooling of thedischarge nozzle is greatly reduced.

Unfortunately, if such a gaseous propellent is used in place of theconventional fluorocarbon propellents in a conventional pressurisedmetering dispenser, the dispenser is unlikely to function correctly. Inorder for the metering to be accurate, the metering chamber must besealed from the main reservoir for the dispenser contents before theoutlet valve is opened. However, this means that the metering chamber isalso sealed from the pressure prevailing in the main reservoir. Thus, ifthe liquid contained in the metering chamber does not include liquifiedadmixed propellent, there will be no pressure within the meteringchamber to drive the metered liquid dose out of the dispenser when theoutlet valve is opened.

Summary of the Invention

According to the present invention there is provided a pressurisedmetering dispenser comprising a main reservoir, a liquid meteringchamber and a gas holding chamber, arranged so that if the mainreservoir is charged with a liquid and a pressurising gas and thedispenser is held in its position of use, the liquid metering chamberwill normally be sealed from the environment and be in communicationwith the main reservoir to receive liquid therefrom and the gas holdingchamber will normally be in communication with the main reservoir toreceive gas therefrom, and during actuation of the dispenser the liquidmetering chamber and the gas holding chamber pass through anintermediate state in which the liquid metering chamber is sealed fromthe external environment and from the main reservoir and the gas holdingchamber is sealed from the main reservoir, and a final state in whichthe liquid metering chamber is open to the environment and the twochambers are in communication with each other but each sealed from themain reservoir.

The liquid metering chamber and the gas holding chamber may also besealed from each other in the intermediate state. In this case, it ispreferable that during the transition from the intermediate state to thefinal state the two chambers are placed in communication before theliquid metering chamber is opened to the environment.

The liquid metering chamber functions in a manner similar to themetering chamber in a prior art dispenser, and its volume determines thevolume of liquid discharged from the dispenser at each actuation. Thegas holding chamber provides a small charge of pressurised gas to drivethe liquid in the liquid metering chamber so that pressurised dispensingof the liquid in the metering chamber occurs. In theory, this advantagecould be obtained by providing means to connect the liquid meteringdispenser to the pressurised gas propellent in the main reservoir, butin this case if the outlet valve was not closed promptly followingdischarge of the liquid from the metering chamber there would be atendency for a complete loss of pressurising propellent from thedispenser. Thus it will be appreciated that the seal required betweenthe gas holding chamber and the main reservoir can be relatively poor,provided that it is sufficient to avoid a general loss of pressurisinggas during a normal dispensing operation. The quality of the sealbetween the liquid metering chamber and the main reservoir is moreimportant, since any tendency for liquid to leak in either directionbetween the liquid melting chamber and the reservoir during dischargewill alter the volume of liquid dispensed.

Advantageously, the dispenser has a longitudingly extending actuatorbody, which includes a discharge passage through which the liquidmetering chamber is connected to the external environment in the finalstate of actuation of the dispenser, and movement of the actuator bodyfrom its normal position through an intermediate position to a finalposition seals the chambers from the reservoir and connects themtogether so as to bring about the said intermediate state of thechambers in the intermediate position of the body and the final state ofthe chambers in the final position of the body. Advantageously, theactuator body is resiliently biased to its normal position and movableagainst the bias to its intermediate position and on to its finalposition. Thus, the actuator body is automatically returned to itsnormal position when it is released, sealing the liquid metering chamberfrom the external environment and connecting the chambers to thereservoir for refilling.

Preferably, the actuator body is moved inwardly into the dispenserduring an actuating stroke from its normal position via its intermediateposition to its final position.

Preferably stop means are provided to limit the travel of the actuatorbody away from the intermediate position beyond the normal and finalpositions.

The liquid metering chamber and the gas holding chamber will normally bespaced from one another, in which case the actuator body convenientlycontains a passageway within it, which opens into the two chambersconnecting them together in the final position of the body.

Preferably, the metering chamber is at the bottom of the dispenser whenthe dispenser is in its position of use, so that in the normal state ofthe chambers liquid from the main reservoir tends to fill the meteringchamber under the influence of gravity.

The liquid metering chamber and the gas holding chamber may be providedspaced apart within a central core of the dispenser, the portion of thecentral core between the two chambers being open to the reservoir andopen to the liquid metering chamber in its normal state to allow liquidto flow into the chamber, and the portion of the central core on theside of the gas holding chamber remote from the liquid metering chamberalso being open to the reservoir and being open to the gas holdingchamber in its normal state to allow gas to flow into the chamber.

Normally, the gas holding chamber will be arranged to be higher than theliquid metering chamber when the dispenser is in its position of use, sothat in the normal state each chamber is open to the portion of thecentral core above it.

If the gas holding chamber is positioned sufficiently high within thedispenser to be above the level of liquid in the reservoir when thedispenser is in its position of use, the gas holding chamber may bearranged to be in communication with the main reservoir at its lowestpoint when in the normal state, to permit the draining from the chamberof any liquid which might accidentally have entered the reservoir whilethe dispenser was in some other position. This drainage connection ispreferably additional to the connection provided for entry of gas intothe gas holding chamber, and is also closed in the intermediate andfinal states of the chamber during actuation of the dispenser.Preferably, during transition from the normal state to the intermediatestate of the chamber, the drainage connection is closed before the gasholding chamber is sealed from the main reservoir.

According to a second aspect of the present invention there is provideda holder for a pressurised metering dispenser, comprising means tosupport a dispenser in its position of use and means to cause relativemovement between the main body of a supported dispenser and an actuatingmember through an actuating stroke, the means for causing relativemovement being itself manually actuable.

Preferably, the holder also comprises means responsive to actuation ofthe means to cause relative movement, which provides a signal when apredetermined number of actuations of the means for causing relativemovement has occured since a dispenser supported in the holder wasplaced in position. The further means may be a counter which provides asignal in the form of a count value in response to each actuation of themeans for causing relative movement. Alternatively, the further meansmay provide a warning signal, as for example a light or a buzzer, onlywhen the predetermined number of actuations has been reached. In eithercase, the further means can be used to warn an operator that thecontents of a dispenser supported in the holder have been almostentirely discharged. Conveniently, means is provided for varyingpredetermined number so that the number of actuations which occur beforethe warning signal is given can be varied to accommodate dispenserscapable of discharging different numbers of metered doses.

Preferably, the holder has mounting means by which it may be mounted ona support surface with a supported dispenser in its position of use.This enables the dispenser to be located more accurately and moresteadily with respect to a dish or the like in to which a dose of liquidis to be discharged than if the holder had to be supported by hand.

The means for causing relative movement between the main body of thedispenser and its actuating member may be powered, and comprise asolonoid or a motor etc. However, it is preferred that the means forcausing relative movement is mechanical and driven by the manualactuation. In a preferred embodiment, this means comprises a lever oneend of which bears on the dispenser and the other end of which is amanually operable trigger.

A holder according to the present invention provides a means of mountingand operating a pressurised metering dispenser in a laboratoryseparately from an analyser such as is disclosed in my earlierapplications. Thus, dispensers might be used mounted in such holdersduring sample preparation and in the performance of tests and analyseswhich do not need to be carried out in analysis apparatus.

In accordance with another aspect of the invention, a modification maybe incorporated in the discharge tube of a dispenser such as notexclusively of the type so far described, by which an accurate samplevolume of a liquid to be analysed can be collected and subsequentlydispensed, together with a metered dose of reagent.

The modification comprises a resiliently biased sleeve which downwardlysurrounds the lower end of the dispenser nozzle and is prevented frompassing beyond the end of the nozzle, and a nozzle extension of knowninternal volume, which extend from the sleeve beyond the dispensernozzle but can be displaced upwardly relative to the nozzle end by anupwardly directed force on the lower end thereof. In use the lower endof the nozzle extension is pushed against the base of a dish orreservoir containing a sample liquid so that the sleeve is fullyretracted and the dispenser is then allowed to rise thereby trapping asmall quantity of the sample liquid in the nozzle extension. The liquidis held in place by surface tension and air pressure.

After removing the dispenser from the liquid, the retained sample can beejected together with a quantity of reagent from the dispenserreservoir, by normal activation of the dispenser. Mixing of the sampleand the reagent occurs during ejection.

Apart from the problems of reagent metering with currently availableequipment, similar problems arise with the requirement to meter samplesfor analysis because the same equipment is used.

However, there is a more serious drawback in that sample carryover orcontamination of a sample by a previous one can be caused by retentionof sample on the walls of the pipette tip. This is overcome by scrappingthe tip after each sample, or by wiping or washing the outside of thetip between samples, but the latter technique still leaves sample insidethe tip. The only other way to avoid carryover is to draw up anddischarge a quantity of cleaning fluid between samples, but this is timeconsuming in manual pipetting, or leads to increased complexity inautomatic samples.

Embodiments of the present invention, are given by way of non-limitativeexample, will now be described with reference to the accompanyingdrawings, in which:

FIG. 1 is a partial sectional view of a pressurised metering dispenserembodying the present invention, in its normal state;

FIG. 2 is a partial sectional view of the dispenser of FIG. 1 in itsfinal state of actuation;

FIG. 3 is an overall view of the dispenser of FIGS. 1 and 2;

FIG. 4 is a partial sectional view of a further dispenser embodying thepresent invention;

FIG. 5 is a side view of a holder embodying the present invention;

FIG. 6 is an end view of the holder of FIG. 5;

FIG. 7 is a cross-section through a discharge tube of a dispenser whichincorporates a modification for collecting accurate sample volumes of aliquid to be analysed; and

FIG. 8 illustrates such a modified dispenser placed in a well containinga liquid of which a sample volume is required to be collected.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

FIGS. 1 to 3 illustrate a pressurised metering dispenser. The meteringand dispensing mechanism is shown in section in FIGS. 1 and 2. In thedispenser, a main body 1 defines a main reservoir 3, which is chargedwith a volume of liquid 5 and pressurised gas 7. The gas 7 functions todrive liquid positively out of the dispenser during discharge, by virtueof its pressure. Accordingly, it is at a pressure above atmospheric,typically about 400 kPa gauge, or 500 kPa absolute. The gas ispreferably selected to be insoluble and chemically unreactive with theliquid 5, and will commonly be nitrogen or argon.

A central core 9 runs within the main body 1 from its mouth sufficientlyfar for its end to be above the level of liquid in the reservoir 3 whenthe dispenser is held mouth downwardly. Preferably, it runs forsubstantially all of the length of the main body 1. Within the centralcore 9, seals 11, 13, 15, 17 define a liquid metering chamber 19 and agas holding chamber 21. In use, the volume of the liquid meteringchamber 19 determines the volume of the metered dose of liquid dispensedfrom the dispenser in a single actuation.

An actuator body 23 is slidably mounted within the central core 9 andprotrudes out through the mouth of the dispenser. It passes through theseals 11, 13, 15, 17 and co-operates with them to provide valves.Additionally, the actuator body 23 contains an internal gas passage 25and an internal liquid discharge passage 27. Thus the actuator body 23also functions as the discharge nozzle of the dispenser.

The actuator body 23 may conveniently be made of nylon or acetol; thevalve seals may be made of nitrite butyl rubber. However, it is possiblethat, for dispensing particularly agressive liquids, it may be preferredto manufacture the body 23 of polypropylene on stainless steel and theseals of fluorocarbon rubber or PTFE based material.

A spring 29 acts on the actuator body 23 to bias it towards a normalposition as shown in FIG. 1. In this position, further movement of theactuator body 23 is prevented by a lower stop flange 31. In thisposition, the chambers 19, 21 are each in their normal states and are incommunication with the respective portions of the central core 9 abovethem.

The portion of the central core 9 between the liquid metering chamber 19and the gas holding chamber 21 is in communication with the mainreservoir 3 by means of apertures 33. Accordingly, the portion of thecentral core 9 immediately above the liquid metering chamber 19 isflooded with liquid 5, so that in the normal state of the liquidmetering chamber as shown in FIG. 1 it also is filled with liquid. Theportion of the central core 9 above the gas holding chamber 21 is incommunication with the main reservoir at its upper end, so that thisportion of the central core 9 is filled with pressurised gas 7.Accordingly, in the normal state the gas holding chamber 21 fills withgas at the pressure prevailing within the main reservoir 3.

In the normal state, both ends of the gas passage 25 are closed by seals13, 17. The upper end of the liquid discharge passage 27 is also closedby seal 17 so that the inside of the dispenser is not in communicationwith the external environment.

To actuate the dispenser, the actuator body 23 is pushed upwardly intothe dispenser in the director of arrow 35, against the action of thespring 29. Conveniently, the actuator body 23 may be moved by pressingagainst an actuation flange 37.

As the actuator body moves upwardly out of its normal position, widerportions of its become level with the seals 11, 15 which define theupper ends of the chambers 19, 21. This closes the passageways throughwhich these chambers were in communication with the remaining portionsof central core 9 and the main reservoir 3. The chambers 19, 21 thusenter a state in which they are sealed from each other and from the mainreservoir 3.

As the actuator body 23 moves further up, the ends of the gas passage 25clear the seals 13, 17 and the liquid metering chamber 19 and the gasholding chamber 21 are placed in communication with each other. Theupper end of the liquid discharge passage 27 remains closed by thelowermost seal 17.

At the end of the actuation stroke, the actuator body 23 reaches itsfinal position, shown in FIG. 2, in which the upper end of the liquiddischarge passage 27 clears the seal 17 and enters the liquid meteringchamber 19. Since the liquid in the liquid metering chamber 19 is atgreater than atmospheric pressure, it begins to flow out of thedispenser through the discharge passage 27. As the liquid flows out ofthe metering chamber 19, the small charge of gas in the gas holdingchamber 21 expands and passes through the gas passage 25 into themetering chamber 19, and thus pressure continues to be applied to theliquid remaining in the metering chamber 19. In this manner, the gasfrom the gas holding chamber 21 drives all of the liquid in the liquidmetering chamber 19 positively out through the discharge passage 27,ensuring that the full metered dose of liquid is dispensed. Finally, thegas is vented to the atmosphere through the discharge passage 27,clearing any remaining liquid out of the passage and removing anydroplets which may have formed at the nozzle of the dispenser.

The actuator body 23 is prevented from moving upwardly beyond its finalactuation position by an upper stop flange 39.

On release of the external force applied to the actuation flange 37, theactuator body 23 moves downwardly under the influence of the spring 29to return to its normal position as shown in FIG. 1, and the chambers19, 21 refill with liquid 5 and gas 7 respectively from the mainreservoir 3.

For ease of manufacturing, the actuator body 23 may be made in twoseparate pieces as is shown in FIGS. 1 and 2. Since the spring 29 actson the upper piece of the actuator body 23, the two pieces are alwayspressed together in all positions of the actuator body 23.

The dispenser may also be provided with a snap-off security nozzle cover40, as shown in broken lines in FIG. 3.

Although the pressurised metering dispenser of FIGS. 1 to 3 is intendedprimarily to dispense a metered dose of liquid as a stream, a suitableknown device may be fitted to the discharge nozzle end of the actuatorbody 23 to divide the discharge liquid into a spray of aerosol of finelydivided droplets. Accordingly, the dispenser may be used for the samepurposes as conventional metering dispensers using fluorocarbonpropellents. This may be desirable from the environmental point of view,as it enables the fluorocarbons to be replaced by less harmfulpropellents.

FIG. 4 shows an alternative dispenser embodying the present invention,in which the gas holding chamber 21 is positioned differently from thearrangement shown in FIGS. 1 and 2. In most respects, the dispenser ofFIG. 4 is the same as the dispenser of FIGS. 1 to 3, and like parts aregiven the same reference numerals. Although not shown in FIG. 4,resilient means such as the spring 29 is provided to urge the actuatorbody 23 downwardly into the normal position, which is illustrated inFIG. 4.

In the embodiment of FIG. 4, the gas holding chamber 21 is positioned atthe end of the dispenser remote from the discharge nozzle and the liquidmetering chamber 19. Accordingly, the actuator body 23 has to extend formost of the length of the dispenser. In order to ensure that it remainscorrectly positioned, an apetured spacer ring 41 is provided within thecentral core 9, intermediate the liquid metering chamber 19 and the gasholding chamber 21. The spacer ring 41 is apertured so that it has nosealing effect and does not tend to support liquid in the core 9 aboveit or alter the pressure on the liquid in the central core 9 below it.

When positioned as shown in FIG. 4, the gas holding chamber 21 is abovethe surface of the liquid 5 when the dispenser is in its position ofuse. This avoids any tendency for liquid 5 to flow into the chamber 21.Additionally, in the normal state the gas holding chamber 21 in FIG. 4is open both at its top and at its bottom, and the seal 13 is so shapedthat the bottom surface of the gas holding chamber 21 slopes downwardlytowards the lower opening. Accordingly, if any liquid 5 should enter thegas holding chamber 21, as may occur if the dispenser is inverted orlaid on its side, the liquid will immediately drain out of the chamber21 through the lower opening when the dispenser is moved to its positionof use. In this way, it is ensured that the gas holding chamber 21 isalways filled with pressurised gas 7 and never contains any liquid 5when the dispenser is actuated in the correct manner, thus ensuring thatthe amount of liquid dispensed is correct and that there is sufficientgas in the gas holding chamber 21 to expel it effectively.

As the actuator body 23 is moved upwardly into the dispenser during anactuating stroke, the lower opening of the gas holding chamber 21 isclosed first, and then the upper opening is also closed, sealing the gasholding chamber 21 from the main reservoir 3. As in the embodiment ofthe FIGS. 1 to 3, after the two chambers 19, 21 have been sealed fromthe main reservoir 3, the ends of the gas passage 25 clear the seals 13,17 and the chambers are placed in communication. Finally, the upper endof the liquid discharge passage 27 clears the lowermost seal 17 and theliquid in the liquid metering chamber 19 is discharged.

In contrast to the arrangement shown in FIG. 3, the central core 9 inthe embodiment of FIG. 4 extends over the entire length of thedispenser, contacting the end surface of the main body 1 remote from thedischarge nozzle, but has apertures 43 around its upper end. Thisfeature may be combined with the mechanism shown in FIGS. 1 and 2, andthe arrangement of the central core 9 shown in FIG. 3 may be used withthe mechanism shown in FIG. 4.

The mechanism shown in FIG. 4 may be varied by removing the opening atthe top of the gas holding chamber 21 so that in its normal state thechamber 21 is only open downwardly. In this case, apertures would haveto be provided in the central core 9 below the level of the gas holdingchamber 21 so that in its normal state the chamber is in communicationwith the main reservoir 3. However, the arrangement shown in FIG. 4 isprefered to this alternative since the upper opening from the gasholding chamber 21 not only serves to place the chamber in communicationwith the main reservoir but acts as a gas inlet during draining of anyliquid which might have entered the gas holding chamber 21. In theabsence of such an upper opening liquid might fail to drain quickly andcompletely from the chamber when the dispenser is moved into itsposition of use.

The main body 1 of the dispenser will normally be metal, but othermaterials such as glass may be used provided that they can withstand thepressure within the dispenser. If the main body 1 is transparent anoperator can see easily how much liquid 5 remains within the dispenserto be dispensed. However, it will often be preferred to make the manbody 1 opaque in order to avoid photochemical effects on the liquid 5from outside light.

The liquid 5 is prepared and introduced into the dispenser duringmanufacture under controlled conditions, so that it is relatively easyto guarantee that its formulation is correct. Because nothing enters thedispenser in use, the liquid is protected from oxidation, contaminationetc, and its sterility is maintained.

Each successive dose is dispensed via the same liquid metering chamber19, so that the repeatability of the doses (lack of variation in volumefrom dose to dose) is good.

FIGS. 5 and 6 show a holder 45 for a pressurised metering dispenser asshown in FIGS. 1 to 4. A dispenser 47 can be removably located insupport means in a supporting arm 49, which holds the dispenser in itsposition of use with the tip of its discharge nozzle raised slightlyabove the surface 51 of the bench on which the holder sits. Thus asample-holding container may be placed under the nozzle of the dispenser47 and a metered dose of the liquid in the dispenser may be dischargedinto the container as part of a sample preparation or analysisprocedure.

The dispenser 47 is actuated by its main body being driven downwardly byone end of an actuating lever 53. The actuating lever 53 is pivoted partway along its length at 55, and its end remote from the dispenser 47forms a manually operable trigger 57. Thus, an operator may grasp theupright portion 59 by hand from the rear with a finger on the trigger57, and may apply a precisely metered dose of liquid from the dispenser47 by squeezing the trigger 57 firmly. The holder 45 remains stablysupported on the surface 51 of the bench or the like by its broad baseportion 61.

At the top rear of the holder 45 there is a counter 63, with its display65 visable to the operator. Operation of the trigger 57 to actuate thedispenser 47 will also depress a button 67 which operates the counter63.

If the counter 63 is reset to zero when a fresh dispenser 47 is fittedinto the holder 45, the counter display 65 can be arranged to displaythe number of actuations of the dispenser and thus the number of metereddoses of liquid discharged from it. This provides the operator with awarning when the total number of metered doses available from thedispenser 47 is being approached. Alternatively, the counter 63 may bearranged to be set to the total number of doses within the dispenser 47when the new dispenser is fitted and arranged to count down so that thedisplay 65 shows how many doses remain within the dispenser 47 to bedischarged.

In addition to warning the operator that a dispenser 47 is nearly emptyby means of the count on the counter display 65, the counter 63 may alsogive some other predetermined warning signal at a specific count, suchas lighting a light, sounding an alarm or moving a shutter into or outof the area of the display 65 to present a warning mark to the operator.

The counter 63 may be electronic and powered by a small battery.Alternatively, it may be entirely mechanical and driven by the movementof the operating button 67.

Preferably, if the counter counts down from the total number of doses inthe dispenser the initial count to which it is set can be varied. If afurther signal is given that the dispenser 47 is nearly empty, inaddition to the count value, then preferably the number of times thetrigger 57 is operated before the further signal is given can be varied.In this way, the operation of the counter 63 may be adapted to differentdispensers 47 containing different numbers of doses.

It is also possible to attach an atomiser or nebulizer to the dispenser,so that the dispensed liquid is dispersed into droplets in like mannerto an aerosol spray.

FIG. 7 shows a section through a discharge tube of a modified dispenserof FIG. 8.

A tip 69 of a sleeve 73 of the dispenser is lowered into contact withthe bottom of a well containing a liquid sample (see FIG. 8), and bypressing down on the dispenser, the lower end of a nozzle of a tube 71slides down through the surrounding tip 69 until it also touches thewell bottom. When the dispenser is withdrawn, a compression spring 75mounted in the sleeve 73 surrounding the nozzle, urges the nozzle endupwards relative to the tip 69 and thus traps a volume of the liquidsample in a chamber 77 formed by the tip 69. The liquid is retained inthe chamber 77 by air pressure and surface tension, in known manner.

The dispenser is then held over a suitable reaction receptacle (notshown) and operated as described hereinbefore, which causes a meteredvolume of reagent in the dispenser contents to travel through a conduit79 in the tube 71 and to mix with and discharge the trapped liquidsample in the chamber 77.

For convenience, the tip 69 and sleeve 73 may be manufactured from aresilient plastics material. The tip 69 is removable by giving a firmpull, but is normally retained on tube 73 by a shoulder at 83 which alsoacts as a seal to prevent or reduce the ingress of air which would causeloss of sample. The shoulder 83 on the tip 69 is also a slidableinterface fit on tube 71 so that a depression is maintained inside tip69 during sampling. The slots 81 in the tip 69 prevent blockage if thetip 69 is placed squarely on the liquid container bottom. The spring 75is substantially weaker than the spring in the dispenser so that thereis less likelihood of discharging the dispenser contents into the samplecontainer during sampling.

As a result of the modifications the dispenser possesses the followingadvantages:

1. The inside of the tip 69 is washed by the metered volume of reagentfrom the dispenser, and it is necessary only to wipe the outside of thetip to ensure zero carryover.

2. The sample volume may be varied easily by fitting a tip of differentlength.

3. A complete cycle of sampling and adding reagent is accomplished inless than half the time required when using existing methods.

4. There is a good mixing of the two liquids during dispensing.

5. Because there is an excess of metered gas during each operation ofthe dispenser, the complete conduit and tip is emptied each time.

6. Manual or automatic equipment would use exactly the samesampler/dispenser.

7. Solid displacement pipetting.

As will be apparent to those skilled in the art, many variations on theillustrated embodiments are possible.

I claim:
 1. A pressurised metering dispenser comprising a mainreservoir, a liquid metering chamber and a gas holding chamber, arrangedso that if the main reservoir is charged with a liquid and apressurising gas and the dispenser is held in its position of use, theliquid metering chamber will normally be sealed from the environment andbe in communication with the main reservoir to receive liquid therefromand the gas holding chamber will normally be in communication with themain reservoir to receive gas therefrom, and during actuation of thedispenser the liquid metering chamber and the gas holding chamber passthrough an intermediate state in which the liquid metering chamber issealed from the external environment and from the main reservoir and thegas holding chamber is sealed from the main reservoir, and a final statein which the liquid metering chamber is open to the environment and thetwo chambers are in communication with each other but each sealed fromthe main reservoir.
 2. A pressurised metering dispenser as claimed inclaim 1 in which the liquid metering chamber and the gas holding chamberare also sealed from each other in the intermediate state.
 3. Apressurised metering dispenser as claimed in claim 2 in which during thetransition from the intermediate state to the final state the twochambers are placed in communication before the liquid metering chamberis opened to the environment.
 4. A pressurised metering dispenser asclaimed in claim 1 in which the dispenser has a longitudingly extendingactuator body, which includes a discharge passage through which theliquid metering chamber is connected to the external environment in thefinal state of actuation of the dispenser, and movement of the actuatorbody from its normal position through an intermediate position to afinal position seals the chambers from the reservoir and connects themtogether so as to bring about the said intermediate state of thechambers in the intermediate position of the body and the final state ofthe chambers in the final position of the body.
 5. A pressurisedmetering dispenser as claimed in claim 4 wherein the actuator body isresiliently biased to its normal position and movable against the biasto its intermediate position and on to its final position, whereby theactuator body is automatically returned to its normal position when itis released, sealing the liquid metering chamber from the externalenvironment and connecting the chambers to the reservoir for refilling.6. A pressurised metering dispenser as claimed in claim 1, in which theliquid metering chamber and the gas holding chamber are spaced from oneanother and the actuator body contains a passageway within it, whichopens into the two chambers connecting them together in the finalposition of the body.
 7. A pressurised metering dispenser as claimed inclaim 1 in which the gas holding chamber is arranged to be higher thanthe liquid metering chamber when the dispenser is in its position ofuse, so that in the normal state each chamber is open to the portion ofthe central core above it.
 8. A pressurised metering dispenser asclaimed in claim 1 and a holder therefor comprising means to support thedispenser in its position of use and means to cause relative movementbetween the main body of the supported dispenser and an actuating memberthrough an actuating stroke, the means for causing relative movementbeing itself manually actuable.
 9. A pressurised metering dispenser asclaimed in claim 1 which includes a nozzle through which reagent isejected during dispensing, and which further includes a sleevesurrounding at least the lower end of the nozzle, the sleeve beingresilitntly displaceable in a direction to expose the lower end of thenozzle, the lower end of the sleeve defining a volume into which aliquid can be drawn by movement of the lower nozzle end in an upwarddirection relative to the lower end of the sleeve.